Frequent Development of Broadly Neutralizing Antibodies in Early Life in a Large Cohort of Children With Human Immunodeficiency Virus.

TitleFrequent Development of Broadly Neutralizing Antibodies in Early Life in a Large Cohort of Children With Human Immunodeficiency Virus.
Publication TypeJournal Article
Year of Publication2022
AuthorsLucier A, Fong Y, Li SHang, Dennis M, Eudailey J, Nelson A, Saunders K, Cunningham CK, McFarland E, McKinney R, M Moody A, LaBranche C, Montefiori D, Permar SR, Fouda GG
JournalJ Infect Dis
Volume225
Issue10
Pagination1731-1740
Date Published2022 May 16
ISSN1537-6613
KeywordsAdult, Antibodies, Neutralizing, Broadly Neutralizing Antibodies, Child, Child, Preschool, Epitopes, HIV Antibodies, HIV Infections, HIV-1, Humans, Immunoglobulin G, Infant
Abstract

BACKGROUND: Recent studies have indicated that broadly neutralizing antibodies (bnAbs) in children may develop earlier after human immunodeficiency virus (HIV) infection compared to adults.

METHODS: We evaluated plasma from 212 antiretroviral therapy-naive children with HIV (1-3 years old). Neutralization breadth and potency was assessed using a panel of 10 viruses and compared to adults with chronic HIV. The magnitude, epitope specificity, and immunoglobulin (Ig)G subclass distribution of Env-specific antibodies were assessed using a binding antibody multiplex assay.

RESULTS: One-year-old children demonstrated neutralization breadth comparable to chronically infected adults, whereas 2- and 3-year-olds exhibited significantly greater neutralization breadth (P = .014). Likewise, binding antibody responses increased with age, with levels in 2- and 3-year-old children comparable to adults. Overall, there was no significant difference in antibody specificities or IgG subclass distribution between the pediatric and adult cohorts. It is interesting to note that the neutralization activity was mapped to a single epitope (CD4 binding site, V2 or V3 glycans) in only 5 of 38 pediatric broadly neutralizing samples, which suggests that most children may develop a polyclonal neutralization response.

CONCLUSIONS: These results contribute to a growing body of evidence suggesting that initiating HIV immunization early in life may present advantages for the development of broadly neutralizing antibody responses.

DOI10.1093/infdis/jiab629
Alternate JournalJ Infect Dis
PubMed ID34962990
PubMed Central IDPMC9113503
Grant ListHHSN275201800001C / HD / NICHD NIH HHS / United States
R01 AI143370 / AI / NIAID NIH HHS / United States
UM1AI068632-15 / MH / NIMH NIH HHS / United States
P30 AI064518 / AI / NIAID NIH HHS / United States
HHSN275201800001I / HD / NICHD NIH HHS / United States
R01 AI122991 / AI / NIAID NIH HHS / United States
UM1 AI106716 / AI / NIAID NIH HHS / United States